Local Consolidative Therapy for Oligometastatic Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Metastatic non-small cell lung cancer (NSCLC) classically portends a poor prognosis and worse overall survival. However, recent advances in modern systemic therapy and the increasing recognition of a distant clinical entity known as “oligometastatic disease”—i.e., a controlled primary tumor and a limited number of distant lesions (≤5 metastases)—have led to paradigm shifts in management. Findings from Phase II randomized clinical trials suggest that aggressive local consolidative therapy (LAT) in the form of surgery or highly conformal radiation, known as stereotactic ablative body radiotherapy (SABR), may help to significantly mitigate disease progression and prolong survival. In this review, we summarize clinical evidence from published and ongoing trials that support the use of LAT/SABR in the treatment of oligometastatic NSCLC. We discuss key findings and caveats to these studies, and we highlight potential considerations and avenues for further investigation in the oligometastatic disease space. ABSTRACT: In the last 20 years, significant strides have been made in our understanding of the biological mechanisms driving disease pathogenesis in metastatic non-small cell lung cancer (NSCLC). Notably, the development and application of predictive biomarkers as well as refined treatment regimens in the form of chemoimmunotherapy and novel targeted agents have led to substantial improvements in survival. Parallel to these remarkable advancements in modern systemic therapy has been a growing recognition of “oligometastatic disease” as a distinct clinical entity—defined by the presence of a controlled primary tumor and ≤5 sites of metastatic disease amenable to local consolidative therapy (LAT), with surgery or stereotactic ablative body radiotherapy (SABR). To date, three randomized studies have provided clinical evidence supporting the use of LAT/SABR in the treatment of oligometastatic NSCLC. In this review, we summarize clinical evidence from these landmark studies and highlight ongoing trials evaluating the use of LAT/SABR in a variety of clinical contexts along the oligometastatic disease spectrum. We discuss important implications and caveats of the available data, including considerations surrounding patient selection and application in routine clinical practice. We conclude by offering potential avenues for further investigation in the oligometastatic disease space.